Sex-related differences in pharmacokinetics and pharmacodynamics of anti-hypertensive drugs

Sex-specific differences in pharmacokinetics and pharmacodynamics have been reported to have important clinical consequences. In this review, some representative sex-specific differences in absorption and transporters (that is, P-glycoprotein (P-gp)), metabolic processes (that is, those that involve cytochrome P450 (CYP)), clearance (Cl) processes (for example, renal excretion or other pharmacokinetic parameters) and involvement of sex hormones (that is, estrogen and testosterone) in the regulation of some metabolic enzymes are introduced for each of the following categories of anti-hypertensive drugs: calcium-channel blockers, angiotensin-receptor blockers and angiotensin-converting enzyme inhibitors, diuretic agents, and β-adrenergic-receptor blockers (β-blockers). In many cases, female sex is a risk factor for adverse effects or attenuated clinical responses because of lower Cl, smaller distribution volumes, higher activity of some metabolic enzymes (especially hepatic CYP3A4), or presence of sex hormones. Additionally, some of these factors often co-contribute to the sex-specific differences. Furthermore, pharmacodynamic variability among individuals is often larger than pharmacokinetic variability; in other words, it could become a predominant determinant of interindividual differences in therapeutic responses. Thus, studies of sex-specific differences in pharmacokinetics and pharmacodynamics should be conducted. However, sex-related disparities in pharmacokinetics may not necessarily correspond to clinically significant differences in therapeutic response. There are still large gaps in our knowledge of sex-specific differences in clinical pharmacology and much more research is needed.